ABSTRACT Zika virus (ZIKV) and Chikungunya virus (CHIKV) are among the new mosquito-transmitted infections that have recently emerged in the Americas (including the continental USA) as major health problems. These diseases are co-endemic, share similar initial symptoms, but differ greatly in disease management and in later stage complications ? birth defects for ZIKV and reactive arthritis (long-term arthralgia) for CHIKV. Reliable diagnostic tools for ZIKV, CHIKV, and other mosquito-borne pathogens are vital for appropriate risk management and therapy; to prevent early misdiagnosis that may worsen later consequences; and for tracking virus transmission patterns. Multiplexed diagnostic tools are urgently needed, but not currently available for use at the point of care. Our long-term objective is to develop an inexpensive, rapid, point of care, multiplexed molecular diagnostic platform for the co-detection of a dozen of mosquito-borne pathogens and the detection of co-infections. In this R21, we take the first steps towards such a system by focusing on molecular detection of ZIKV and CHIKV in blood. Our system will accept a raw sample, carry out sample preparation and a new two-stage isothermal-isothermal enzymatic amplification, and report results. Our device can be used in the clinic, doctor office, and at home with minimal instrumentation and (optionally) without electrical power. To enable quantification and surveillance, the system can optionally interface with a smartphone for signal detection, processing, and transmission. The proposed platform is versatile, can be readily modified to address emerging threats, expanded to detect additional targets, and adapted to operate with various clinical specimens.